We are utilizing the Chinese hamster ovary (CHO) fibroblast to study the genetics and biochemistry of some aspects of the behavior of cultured cells. Our work has emphasized morphology and its relationship to growth control, and response to cyclic AMP and transforming viruses. We have isolated a variety of different mutants with altered microtubules which express mutated Alpha- or Beta-tubulin subunits. These mutants are defective in spindle formation because the mutant tubulins are incorporated into spindle microtubules. We have also established two cell systems for examining the ways in which AMP can positively and negatively regulate cell growth. CHO cell growth is inhibited by cAMP; mutants selected for resistance to growth inhibition have defective cAMP dependent protein kinases (cAdepPK). Analysis of these mutants and their revertants indicates that all known cAMP effects are blocked by the kinase mutations. In contrast, drugs such as interferon and tumor promoters which raise cAMP levels, are still able to exert their effects in cAMP-resistant CHO cells, indicating that the major mechanism of action of these drugs is independent of cAdepPK. We have used DNA from cells carrying dominant cAMP-resistant defects to transfer the cAMP-resistance phenotype to sensitive cells as a first step toward the cloning of the genes which make our mutants cAMP-resistant. CHO cells malignantly transformed by RSV are also cAMP-resistant. Formation of tumors by CHO-RSV cells is dependent on prior treatment with cholera toxin which raises cAMP levels within the cells. This increased tumorigenicity is an example of positive regulation of cell growth by cAMP which correlates with phosphorylation of pp60src and activation of its tyrosine kinase activity.